Rational Design of Crystallization‐Induced‐Emission Probes To Detect Amorphous Protein Aggregation in Live Cells

Unlike amyloid aggregates, amorphous protein aggregates with no defined structures have been challenging to target and detect in a complex cellular milieu. In this study, we rationally designed sensors of amorphous protein aggregation from aggregation‐induced‐emission probes (AIEgens). Utilizing dic...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2021-07, Vol.60 (29), p.16067-16076
Main Authors: Shen, Di, Jin, Wenhan, Bai, Yulong, Huang, Yanan, Lyu, Haochen, Zeng, Lianggang, Wang, Mengdie, Tang, Yuqi, Wan, Wang, Dong, Xuepeng, Gao, Zhenming, Piao, Hai‐Long, Liu, Xiaojing, Liu, Yu
Format: Article
Language:English
Subjects:
Agglomeration
Aggregates
aggregation-induced emission
Amyloid
Crystallization
Emission
Emissions
Fluorescence
Fluorescent Dyes - chemistry
Humans
Indoor environments
Mimicry
Probes
Protein Aggregates
protein aggregation
protein homeostasis
Protein interaction
Proteins
Proteomes
Selective binding
Sensors
Spectral sensitivity
Target detection
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Summary:Unlike amyloid aggregates, amorphous protein aggregates with no defined structures have been challenging to target and detect in a complex cellular milieu. In this study, we rationally designed sensors of amorphous protein aggregation from aggregation‐induced‐emission probes (AIEgens). Utilizing dicyanoisophorone as a model AIEgen scaffold, we first sensitized the fluorescence of AIEgens to a nonpolar and viscous environment mimicking the interior of amorphous aggregated proteins. We identified a generally applicable moiety (dimethylaminophenylene) for selective binding and fluorescence enhancement. Regulation of the electron‐withdrawing groups tuned the emission wavelength while retaining selective detection. Finally, we utilized the optimized probe to systematically image aggregated proteome upon proteostasis network regulation. Overall, we present a rational approach to develop amorphous protein aggregation sensors from AIEgens with controllable sensitivity, spectral coverage, and cellular performance. Aggregation‐induced‐emission dyes were rationally designed to detect amorphous protein aggregation with controllable sensitivity, color, and cellular performance (see structure). A dimethylaminophenylene group enabled selective binding and fluorescence enhancement, and the emission wavelength could be tuned by altering the electron‐withdrawing groups on the other ring while retaining selective detection.
ISSN:1433-7851
1521-3773
1521-3773
DOI:10.1002/anie.202103674